Non-destructive cellular and Molecular Imaging of in vivo systems is critical to the understanding of biologic processes involved in cancer. These imaging strategies are ideal for longitudinal studies that can assess the mechanism of action and the consequence of interventions and the monitoring of disease progression or regression in living animal. More importantly, these in vivo imaging tools can be translated to human patients. Because of the need to evaluate the efficacy of anti-angiogenesis agents using functional end-points, and because of the strong basic research program in this field at our institution, we have chosen angiogenesis as the principle focus for the proposed possible projects. This proposal offers 2 new ideas to molecular and cellular targeting. It introduces ultrasound imaging as a potentially powerful technique that can be applied worldwide as well as at the bedside and in the operating room. Because angiogenesis and apoptosis provide surface markers at the endothelial surface that are accessible to the vascular space and therefore targetable by microbubble ultrasound contrast agents, we have proposed a potentially feasible study to test this hypothesis. This proposal also introducers the concept of targeted cellular killing by loading the imaging probe with a heavy metal rather than a positron or an MRI or an optical agent. In effect one can image and then kill the cells that are expressing a specific gene by optimal external radiation concentrates the energy in the cells of interest. UCSD and the San Diego community including the Salk and Scripps Institutes as well as other cancer research institutes and biotechnology companies, have broad expertise and substantial laboratory resources for basic cancer research. As an institution we have recruited a critical mass of imaging and have committed resources to build a PET and MRI program. A PET center including a cyclotron will come on line by the end of 2000 and an MRI research facility with 4 needed to create and foster interaction and collaboration among the investigators and to train and develop new talent in molecular biology with imaging expertise and imager with molecular biology expertise. We have the commitment from the Director of the Cancer Center and the Dean to develop the Imaging Center into a comprehensive imaging program to qualify for the P50 grant in 2 years.